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        RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination

        Matthews, Adam G. W.,Kuo, Alex J.,Ramó,n-Maiques, Santiago,Han, Sunmi,Champagne, Karen S.,Ivanov, Dmitri,Gallardo, Mercedes,Carney, Dylan,Cheung, Peggie,Ciccone, David N.,Walter, Kay L.,Utz, Pau Nature Publishing Group 2007 Nature Vol.450 No.7172

        Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post-translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2—an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen-receptor gene assembly—contains a plant homeodomain (PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). The high-resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3-recognition by RAG2. Mutations that abrogate RAG2’s recognition of H3K4me3 severely impair V(D)J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue (W453) that constitutes a key structural component of the K4me3-binding surface and is essential for RAG2’s recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease.

      • Improved biocompatibility of hydroxyapatite thin film prepared by aerosol deposition

        Park, Dong-Soo,Kim, In-Sook,Kim, Hyeongil,Chou, Alex Hung Kuo,Hahn, Byung-Dong,Li, Long-Hao,Hwang, Soon-Jung Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of biomedical materials research. Part B, Vol.94 No.2

        <P>Technical development for an efficient coating of bioactive materials improves the characteristics of a fully functional implant. The aim of this study was to investigate the osteoinductive effect of a newly developed hydroxyapatite (HA)-coating technique using aerosol deposition without post-heat treatment [room temperature (RT) group] on the titanium (Ti) dental implant in vitro and in vivo, compared with that of HA coating with post-heat treatment (HT-400 group) or machined surface (control group). Cell proliferation or attachment on the HA-coated Ti surface was assessed using tetrazolium salt, WST-8 or scanning electron microscopy (SEM). Human osteoblasts (HOB) on RT group were well attached and grew alike in the control or HT-400 group. The alkaline phosphatase activity of HOB cultured on RT and HT-400 group was significantly higher than the control group (p < 0.05). Evaluation by SEM, TEM, and XRD demonstrated that aerosol deposition facilitated HA particles to form a dense and uniform HA layer in the RT group despite no post-heating. In a rabbit tibia model (n = 3), the ratios of bone implant contact and bone area in the RT group (49.88%, 86.05%) were greater than in the HT-400 group (38.82%, 77.34%) or the control (28.31%, 73.86%). The finding of this study showed that the HA coating using aerosol deposition without post-heat treatment has a good biocompatibility, and provide a promoting strategy to enhance osseointegration in the application of the dental implant. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.</P>

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        Implementation of clinical practice changes by experienced anesthesiologists after simulationbased ultrasound-guided regional anesthesia training

        T. Edward Kim,Edward R. Mariano,Toni Ganaway,T. Kyle Harrison,Steven K. Howard,Cynthia Shum,Alex Kuo 대한마취통증의학회 2017 Korean Journal of Anesthesiology Vol.70 No.3

        Background: Anesthesiologists who have finished formal training and want to learn ultrasound-guided regional anesthesia (UGRA) commonly attend 1 day workshops. However, it is unclear whether participation actually changes clinical practice. We assessed change implementation after completion of a 1 day simulation-based UGRA workshop. Methods: Practicing anesthesiologists who participated in a 1 day UGRA course from January 2012 through May 2014 were surveyed. The course consisted of clinical observation of UGRA procedures, didactic lectures, ultrasound scanning, hands-on perineural catheter placement, and mannequin simulation. The primary outcome was the average number of UGRA blocks per month reported at follow-up versus baseline. Secondary outcomes included preference for ultrasound as the nerve localization technique, ratings of UGRA teaching methods, and obstacles to performing UGRA. Results: Survey data from 46 course participants (60% response rate) were included for analysis. Participants were (median [10th–90th percentile]) 50 (37–63) years old, had been in practice for 17 (5–30) years, and were surveyed 27 (10–34) months after their UGRA training. Participants reported performing 24 (4–90) blocks per month at follow-up compared to 10 (2–24) blocks at baseline (P < 0.001). Compared to baseline, more participants at follow-up preferred ultrasound for nerve localization. The major obstacle to implementing UGRA in clinical practice was time pressure. Conclusions: Participation in a 1 day simulation-based UGRA course may increase UGRA procedural volume by practicing anesthesiologists.

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